Germ theory of disease

The germ theory of disease states that some diseases are caused by microorganisms. These small organisms, too small to see without magnification, invade humans, animals, and other living hosts. Their growth and reproduction within their hosts can cause a disease. "Germ" may refer to not just a bacterium but to any type of microorganisms, especially one which causes disease, such as protist, fungus, virus, prion, or viroid.[1] Microorganisms that cause disease are called pathogens, and the diseases they cause are called infectious diseases. Even when a pathogen is the principal cause of a disease, environmental and hereditary factors often influence the severity of the disease, and whether a particular host individual becomes infected when exposed to the pathogen.

The germ theory was proposed by Girolamo Fracastoro in 1546, but scientific evidence in support of this accumulated slowly and Galen'smiasma theory remained dominant among scientists and doctors. A transitional period began in the late 1850s as the work of Louis Pasteur and Robert Koch provided convincing evidence; by 1880, miasma theory was still competing with the germ theory of disease. Eventually, a "golden era" of bacteriology ensued, in which the theory quickly led to the identification of the actual organisms that cause many diseases.[2][3]Viruses were discovered in the 1890s.

The miasma theory of disease transmission held that diseases such as cholera, chlamydia or the Black Death were caused by a miasma (μίασμα, Ancient Greek: "pollution"), a noxious form of "bad air". The theory held that the origin of these epidemic diseases was a miasma, emanating from rotting organic matter.[4] Miasma was considered to be a poisonous vapor or mist filled with particles from decomposed matter (miasmata) that caused illnesses. The miasmatic position was that diseases were the product of environmental factors such as contaminated water, foul air, and poor hygienic conditions. Such infection was not passed between individuals but would affect individuals within the locale that gave rise to such vapors. It was identifiable by its foul smell.

This was the predominant theory of disease transmission before the germ theory of disease took hold in the last decade of the 19th century.

There is some evidence that the Ancient Romans had a germ theory of disease that was later forgotten. Notably, Marcus Terentius Varro wrote, in his 'Rerum rusticarum libri III': "Precautions must also be taken in the neighborhood of swamps [...] because there are bred certain minute creatures which cannot be seen by the eyes, which float in the air and enter the body through the mouth and nose and there cause serious diseases."

Girolamo Fracastoro proposed in 1546 that epidemic diseases are caused by transferable seed-like entities that transmit infection by direct or indirect contact, or even without contact over long distances.

Italian physician Francesco Redi provided early evidence against spontaneous generation. He devised an experiment in 1668 in which he used three jars. He placed a meatloaf and egg in each of the three jars. He had one of the jars open, another one tightly sealed, and the last one covered with gauze. After a few days, he observed that the meatloaf in the open jar was covered by maggots, and the jar covered with gauze had maggots on the surface of the gauze. However, the tightly sealed jar had no maggots inside or outside it. He also noticed that the maggots were found only on surfaces that were accessible by flies. From this he concluded that spontaneous generation is not a plausible theory.

Microorganisms are said to be first directly observed in the 1670s by Anton van Leeuwenhoek, an early pioneer in microbiology. Yet Athanasius Kircher may have done so prior. "When Rome was struck by the bubonic plague in 1656, Kircher spent days on end caring for the sick. Searching for a cure, Kircher observed microorganisms under the microscope and invented the germ theory of disease, which he outlined in his Scrutinium pestis physico-medicum (Rome 1658)."[5] Building on Leeuwenhoek's work, physician Nicolas Andry argued in 1700 that microorganisms he called "worms" were responsible for smallpox and other diseases.[6]

In 1720, Richard Bradley theorised that plague and 'all pestilential distempers' were caused by 'poisonous insects', living creatures viewable only with the help of microscopes.[7]

In a 1767 report to the College of Physicians in London, John Zephaniah Holwell mentions the practice of Smallpox vaccinations by Ayurvedic doctors and their explanations of the cause of the disease. According to his report, the Ayurvedic doctors explained to him that disease is caused by 'multitudes of imperceptible animalculae (microorganisms) floating in the atmosphere; that these are the cause of all epidemical diseases'. They further explained to him that they (microorganisms) circulate in and out of the bodies of all animals during respiration and that the severity of disease is proportional to the air charged with the animalculae, and the quantity of them received with the food'.[8] He was convinced by the physicians that when the disease of smallpox has run its course either naturally or after inoculations in its weak form, the patients were safe. The major difference between the two being that while natural infections are mostly fatal, the inoculations were merely an inconvenience. According to Henderson and Moss the practice of this method of inoculation has been prevalent in India from just before 1000 A.D.[9]

The Italian Agostino Bassi was the first person to prove that a disease was caused by a microorganism when he conducted a series of experiments between 1808 and 1813, demonstrating that a "vegetable parasite" caused a disease in silkworms known as calcinaccio. This disease was devastating the French silk industry at the time. The "vegetable parasite" is now known to be a fungus pathogenic to insects called Beauveria bassiana (named after Bassi).

Ignaz Semmelweis was a Hungarianobstetrician working at the Vienna General Hospital (Allgemeines Krankenhaus) in 1847, when he noticed the dramatically high incidence of death from puerperal fever among women who delivered at the hospital with the help of the doctors and medical students. Births attended by the midwives were relatively safe. Investigating further, Semmelweis made the connection between puerperal fever and examinations of delivering women by doctors, and further realized that these physicians had usually come directly from autopsies. Asserting that puerperal fever was a contagious disease and that matter from autopsies were implicated in its development, Semmelweis made doctors wash their hands with chlorinated lime water before examining pregnant women, thereby reducing mortality from childbirth from 18% to 2.2% at his hospital. Nevertheless, he and his theories were rejected by most of the contemporary medical establishment.

Original map by John Snow showing the clusters of cholera cases in the London epidemic of 1854

John Snow was a skeptic of the then-dominant miasma theory. Even though the germ theory of disease pioneered by Girolamo Fracastoro had not yet achieved full development or widespread currency, Snow demonstrated a clear understanding of germ theory in his writings. He first published his theory in an 1849 essay On the Mode of Communication of Cholera, in which he correctly suggested that the fecal-oral route was the mode of communication, and that the disease replicated itself in the lower intestines. He even proposed in his 1855 edition of the work, that the structure of cholera was that of a cell.

Having rejected effluvia and the poisoning of the blood in the first instance, and being led to the conclusion that the disease is something that acts directly on the alimentary canal, the excretions of the sick at once suggest themselves as containing some material which being accidentally swallowed might attach itself to the mucous membrane of the small intestines, and there multiply itself by appropriation of surrounding matter, in virtue of molecular changes going on within it, or capable of going on, as soon as it is placed in congenial circumstances.

— John Snow (1849)

Snow's 1849 recommendation that water be "filtered and boiled before it is used" is one of the first practical applications of germ theory in the area of public health and is the antecedent to the modern boil water advisory.

In 1855 he published a second edition of his article, documenting his more elaborate investigation of the effect of the water supply in the Soho, London epidemic of 1854.

By talking to local residents, he identified the source of the outbreak as the public water pump on Broad Street (now Broadwick Street). Although Snow's chemical and microscope examination of a water sample from the Broad Street pump did not conclusively prove its danger, his studies of the pattern of the disease were convincing enough to persuade the local council to disable the well pump by removing its handle. This action has been commonly credited as ending the outbreak, but Snow observed that the epidemic may have already been in rapid decline.[10]

Snow later used a dot map to illustrate the cluster of cholera cases around the pump. He also used statistics to illustrate the connection between the quality of the water source and cholera cases. He showed that the Southwark and Vauxhall Waterworks Company was taking water from sewage-polluted sections of the Thames and delivering the water to homes, leading to an increased incidence of cholera. Snow's study was a major event in the history of public health and geography. It is regarded as one of the founding events of the science of epidemiology.

Later, researchers discovered that this public well had been dug only three feet from an old cesspit, which had begun to leak fecal bacteria.[citation needed] The diapers of a baby, who had contracted cholera from another source, had been washed into this cesspit. Its opening was originally under a nearby house, which had been rebuilt farther away after a fire. The city had widened the street and the cesspit was lost. It was common at the time to have a cesspit under most homes. Most families tried to have their raw sewage collected and dumped in the Thames to prevent their cesspit from filling faster than the sewage could decompose into the soil.

After the cholera epidemic had subsided, government officials replaced the handle on the Broad Street pump. They had responded only to the urgent threat posed to the population, and afterward they rejected Snow's theory. To accept his proposal would have meant indirectly accepting the fecal-oral method transmission of disease, which they dismissed as "too depressing."[11]

The more formal experiments on the relationship between germ and disease were conducted by Louis Pasteur between 1860 and 1864. He discovered the pathology of the puerperal fever[12] and the pyogenic vibrio in the blood, and suggested using boric acid to kill these microorganisms before and after confinement.

Louis Pasteur’s pasteurization experiment illustrates the fact that the spoilage of liquid was caused by particles in the air rather than the air itself. These experiments were important pieces of evidence supporting the idea of Germ Theory of Disease.

Pasteur further demonstrated between 1860 and 1864 that fermentation and the growth of microorganisms in nutrient broths did not proceed by spontaneous generation. He exposed freshly boiled broth to air in vessels that contained a filter to stop all particles passing through to the growth medium, and even with no filter at all, with air being admitted via a long tortuous tube that would not pass dust particles. Nothing grew in the broths: therefore the living organisms that grew in such broths came from outside, as spores on dust, rather than being generated within the broth.

Pasteur discovered that another serious disease of silkworms, pébrine, was caused by a small microscopic organism now known as Nosema bombycis (1870). Pasteur saved the silk industry in France by developing a method to screen silkworms eggs for those that are not infected, a method that is still used today to control this and other silkworm diseases.

Robert Koch is known for developing four basic criteria (known as Koch's postulates) for demonstrating, in a scientifically sound manner, that a disease is caused by a particular organism. These postulates grew out of his seminal work with anthrax using purified cultures of the pathogen that had been isolated from diseased animals.

Koch's postulates were developed in the 19th century as general guidelines to identify pathogens that could be isolated with the techniques of the day.[13] Even in Koch's time, it was recognized that some infectious agents were clearly responsible for disease even though they did not fulfill all of the postulates.[14][15] Attempts to rigidly apply Koch's postulates to the diagnosis of viral diseases in the late 19th century, at a time when viruses could not be seen or isolated in culture, may have impeded the early development of the field of virology.[16][17] Currently, a number of infectious agents are accepted as the cause of disease despite their not fulfilling all of Koch's postulates.[18] Therefore, while Koch's postulates retain historical importance and continue to inform the approach to microbiologic diagnosis, fulfillment of all four postulates is not required to demonstrate causality.

Koch's postulates have also influenced scientists who examine microbial pathogenesis from a molecular point of view. In the 1980s, a molecular version of Koch's postulates was developed to guide the identification of microbial genes encoding virulence factors.[19]

Koch's postulates:

The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms.

The microorganism must be isolated from a diseased organism and grown in pure culture.

The cultured microorganism should cause disease when introduced into a healthy organism.

The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

However, Koch abandoned the universalist requirement of the first postulate altogether when he discovered asymptomatic carriers of cholera[20] and, later, of typhoid fever. Asymptomatic or subclinical infection carriers are now known to be a common feature of many infectious diseases, especially viruses such as polio, herpes simplex, HIV, and hepatitis C. As a specific example, all doctors and virologists agree that poliovirus causes paralysis in just a few infected subjects, and the success of the polio vaccine in preventing disease supports the conviction that the poliovirus is the causative agent.

The third postulate specifies "should", not "must", because as Koch himself proved in regard to both tuberculosis and cholera,[14] not all organisms exposed to an infectious agent will acquire the infection. Noninfection may be due to such factors as general health and proper immune functioning; acquired immunity from previous exposure or vaccination; or genetic immunity, as with the resistance to malaria conferred by possessing at least one sickle cell allele.

The second postulate may also be suspended for certain microorganisms or entities that cannot (at the present time) be grown in pure culture, such as prions responsible for Creutzfeldt–Jakob disease.[21] In summary, a body of evidence that satisfies Koch's postulates is sufficient but not necessary to establish causation.

In the 1870s, Joseph Lister was instrumental in developing practical applications of the germ theory of disease with respect to sanitation in medical settings and aseptic surgical techniques—partly through the use of carbolic acid (phenol) as an antiseptic.

^"The History of the Germ Theory". The British Medical Journal. 1 (1415): 312. 1888.

^Melvin Santer, ‘Richard Bradley: A Unified, Living Agent Theory of the Cause of Infectious Diseases of Plants, Animals, and Humans in the First Decades of the 18th Century’, in Perspectives in Biology and Medicine, Volume 52, Number 4, Autumn, 2009, pp. 566-578

^John Snow (1849). On the Mode of Communication of Cholera. London: J. Churchill. There is no doubt that the mortality was much diminished, as I said before, by the flight of the population, which commenced soon after the outbreak; but the attacks had so far diminished before the use of the water was stopped, that it is impossible to decide whether the well still contained the cholera poison in an active state, or whether, from some cause, the water had become free from it